Abstract

Positive-strand RNA viruses universally remodel host intracellular membranes to form membrane-bound viral replication complexes, where viral offspring RNAs are synthesized. In the majority of cases, viral replication proteins are targeted to and play critical roles in the modulation of the designated organelle membranes. Many viral replication proteins do not have transmembrane domains, but contain single or multiple amphipathic alpha-helices. It has been conventionally recognized that these helices serve as an anchor for viral replication protein to be associated with membranes. We report here that a peptide representing the amphipathic α-helix at the N-terminus of the poliovirus 2C protein not only binds to liposomes, but also remodels spherical liposomes into tubules. The membrane remodeling ability of this amphipathic alpha-helix is similar to that recognized in other amphipathic alpha-helices from cellular proteins involved in membrane remodeling, such as BAR domain proteins. Mutations affecting the hydrophobic face of the amphipathic alpha-helix severely compromised membrane remodeling of vesicles with physiologically relevant phospholipid composition. These mutations also affected the ability of poliovirus to form plaques indicative of reduced viral replication, further underscoring the importance of membrane remodeling by the amphipathic alpha-helix in possible relation to the formation of viral replication complexes.

Highlights

  • Positive-strand RNA viruses [(+)RNA viruses] are the largest among all viral classes infecting eukaryotes, and include numerous important pathogens infecting humans, animals, and plants.A hallmark of (+)RNA virus replication is its dependence on host intracellular membranes to assemble functional viral replication complexes (VRCs) or replication organelles [1,2]

  • We evaluated the role of an 18 amino acid peptide (2C-wt) from the N-terminal region of the poliovirus 2C protein

  • These viruses replicate in designated organelle membranes, where viral replication proteins, in the majority of cases, facilitate or induce membrane rearrangements

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Summary

Introduction

Positive-strand RNA viruses [(+)RNA viruses] are the largest among all viral classes infecting eukaryotes, and include numerous important pathogens infecting humans, animals, and plants.A hallmark of (+)RNA virus replication is its dependence on host intracellular membranes to assemble functional viral replication complexes (VRCs) or replication organelles [1,2]. C (HCV) [7], and beet black scotch virus [8] at the ER, tomato bushy stunt virus at peroxisome [9], and poliovirus at the interface of the ER and Golgi apparatus [10], among others. It is not well understood how viral replication proteins are targeted to specific organelles and how they interact with cellular membranes to remodel the membranes to form VRCs. Multiple viral replication proteins have been reported to rearrange cellular membranes to form

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